The Wellcome Trust Lecture. Infection and disease in lymphatic filariasis: an immunological perspective.

The basic tenet of the immunological perspective of filarial disease is that differential immune responsiveness among individuals exposed to infection results in the different clinical manifestations that develop. The mechanisms involved in this differential responsiveness appear to reflect different T-cell cytokine response patterns. Asymptomatic patients with the clinically silent presentation of 'asymptomatic microfilaraemia', who have been previously described as being 'immunosuppressed' with respect to their generating pro-inflammatory (Th1-type) immune responses to parasite antigen, are now recognized to be fully responsive to parasite antigen but to produce cytokines and mediators that have primarily anti-inflammatory (Th2-like) effects. Studies with immunodeficient mice have indicated the existence of two alternative pathways to the development of lymphatic pathology: one dependent on the induction of inflammatory reactions by the host immune response, the other entirely independent of the immune system and reflecting the direct actions of the parasite or its products on the lymphatics. As histopathology of affected human lymphatics is consistent with this hypothesis, it may be that the lymphatic pathology seen normally in the amicrofilaraemic, highly immunoresponsive infected patients derives from inflammation induced by immune responses to parasite antigen, whereas the lymphatic pathology sometimes seen coexisting with the 'immunosuppressed' state of asymptomatic microfilaraemia actually reflects lymphatic damage that is not immunologically mediated. Though little information exists about the 'natural history' of lymphatic filariasis, there is no evidence for an inevitable progression from one clinical form to another.(ABSTRACT TRUNCATED AT 250 WORDS)